PKD1 is a potential biomarker and therapeutic target in triple-negative breast cancer
<p dir="ltr">Protein Kinase D1 (PKD1) is a serine/threonine kinase encoded by the <i>PRKD1</i> gene. PKD1 has been previously shown to be a prognostic factor in ERα+ tamoxifen-resistant breast tumors and PKD1 overexpression confers estrogen independence to ERα+ MCF7 cells...
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2018
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| _version_ | 1864513513012068352 |
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| author | Caroline Spasojevic (3619418) |
| author2 | Elisabetta Marangoni (655592) Sophie Vacher (233965) Franck Assayag (3157383) Didier Meseure (666209) Sophie Château-Joubert (11410163) Martine Humbert (252271) Manale Karam (3619412) Jean Marc Ricort (18696934) Christian Auclair (140039) Marie Regairaz (1465762) Ivan Bièche (3492) |
| author2_role | author author author author author author author author author author author |
| author_facet | Caroline Spasojevic (3619418) Elisabetta Marangoni (655592) Sophie Vacher (233965) Franck Assayag (3157383) Didier Meseure (666209) Sophie Château-Joubert (11410163) Martine Humbert (252271) Manale Karam (3619412) Jean Marc Ricort (18696934) Christian Auclair (140039) Marie Regairaz (1465762) Ivan Bièche (3492) |
| author_role | author |
| dc.creator.none.fl_str_mv | Caroline Spasojevic (3619418) Elisabetta Marangoni (655592) Sophie Vacher (233965) Franck Assayag (3157383) Didier Meseure (666209) Sophie Château-Joubert (11410163) Martine Humbert (252271) Manale Karam (3619412) Jean Marc Ricort (18696934) Christian Auclair (140039) Marie Regairaz (1465762) Ivan Bièche (3492) |
| dc.date.none.fl_str_mv | 2018-05-01T00:00:00Z |
| dc.identifier.none.fl_str_mv | 10.18632/oncotarget.25292 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/PKD1_is_a_potential_biomarker_and_therapeutic_target_in_triple-negative_breast_cancer/25930939 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Oncology and carcinogenesis PKC PKD protein kinase D1 triple-negative breast cancer |
| dc.title.none.fl_str_mv | PKD1 is a potential biomarker and therapeutic target in triple-negative breast cancer |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Protein Kinase D1 (PKD1) is a serine/threonine kinase encoded by the <i>PRKD1</i> gene. PKD1 has been previously shown to be a prognostic factor in ERα+ tamoxifen-resistant breast tumors and PKD1 overexpression confers estrogen independence to ERα+ MCF7 cells. In the present study, our goal was to determine whether PKD1 is a prognostic factor and/or a relevant therapeutic target in breast cancer. We analyzed <i>PRKD1</i> mRNA levels in 527 primary breast tumors. We found that high <i>PRKD1</i> mRNA levels were significantly and independently associated with a low metastasis-free survival in the whole breast cancer population and in the triple-negative breast cancer (TNBC) subtype specifically. High <i>PRKD1</i> mRNA levels were also associated with a low overall survival in TNBC. We identified novel PKD1 inhibitors and assessed their antitumor activity <i>in vitro</i> in TNBC cell lines and <i>in vivo</i> in a TNBC patient-derived xenograft (PDX) model. Pharmacological inhibition and siRNA-mediated depletion of PKD1 reduced colony formation in MDA-MB-436 TNBC cells. PKD1 inhibition also reduced tumor growth <i>in vivo</i> in a TNBC PDX model. Together, these results establish PKD1 as a poor prognostic factor and a potential therapeutic target in TNBC.</p><h2>Other Information</h2><p dir="ltr">Published in: Oncotarget<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.18632/oncotarget.25292" target="_blank">https://dx.doi.org/10.18632/oncotarget.25292</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_0fc0916a744ab773aae9abe93359037b |
| identifier_str_mv | 10.18632/oncotarget.25292 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25930939 |
| publishDate | 2018 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | PKD1 is a potential biomarker and therapeutic target in triple-negative breast cancerCaroline Spasojevic (3619418)Elisabetta Marangoni (655592)Sophie Vacher (233965)Franck Assayag (3157383)Didier Meseure (666209)Sophie Château-Joubert (11410163)Martine Humbert (252271)Manale Karam (3619412)Jean Marc Ricort (18696934)Christian Auclair (140039)Marie Regairaz (1465762)Ivan Bièche (3492)Biomedical and clinical sciencesOncology and carcinogenesisPKCPKDprotein kinase D1triple-negative breast cancer<p dir="ltr">Protein Kinase D1 (PKD1) is a serine/threonine kinase encoded by the <i>PRKD1</i> gene. PKD1 has been previously shown to be a prognostic factor in ERα+ tamoxifen-resistant breast tumors and PKD1 overexpression confers estrogen independence to ERα+ MCF7 cells. In the present study, our goal was to determine whether PKD1 is a prognostic factor and/or a relevant therapeutic target in breast cancer. We analyzed <i>PRKD1</i> mRNA levels in 527 primary breast tumors. We found that high <i>PRKD1</i> mRNA levels were significantly and independently associated with a low metastasis-free survival in the whole breast cancer population and in the triple-negative breast cancer (TNBC) subtype specifically. High <i>PRKD1</i> mRNA levels were also associated with a low overall survival in TNBC. We identified novel PKD1 inhibitors and assessed their antitumor activity <i>in vitro</i> in TNBC cell lines and <i>in vivo</i> in a TNBC patient-derived xenograft (PDX) model. Pharmacological inhibition and siRNA-mediated depletion of PKD1 reduced colony formation in MDA-MB-436 TNBC cells. PKD1 inhibition also reduced tumor growth <i>in vivo</i> in a TNBC PDX model. Together, these results establish PKD1 as a poor prognostic factor and a potential therapeutic target in TNBC.</p><h2>Other Information</h2><p dir="ltr">Published in: Oncotarget<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.18632/oncotarget.25292" target="_blank">https://dx.doi.org/10.18632/oncotarget.25292</a></p>2018-05-01T00:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.18632/oncotarget.25292https://figshare.com/articles/journal_contribution/PKD1_is_a_potential_biomarker_and_therapeutic_target_in_triple-negative_breast_cancer/25930939CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/259309392018-05-01T00:00:00Z |
| spellingShingle | PKD1 is a potential biomarker and therapeutic target in triple-negative breast cancer Caroline Spasojevic (3619418) Biomedical and clinical sciences Oncology and carcinogenesis PKC PKD protein kinase D1 triple-negative breast cancer |
| status_str | publishedVersion |
| title | PKD1 is a potential biomarker and therapeutic target in triple-negative breast cancer |
| title_full | PKD1 is a potential biomarker and therapeutic target in triple-negative breast cancer |
| title_fullStr | PKD1 is a potential biomarker and therapeutic target in triple-negative breast cancer |
| title_full_unstemmed | PKD1 is a potential biomarker and therapeutic target in triple-negative breast cancer |
| title_short | PKD1 is a potential biomarker and therapeutic target in triple-negative breast cancer |
| title_sort | PKD1 is a potential biomarker and therapeutic target in triple-negative breast cancer |
| topic | Biomedical and clinical sciences Oncology and carcinogenesis PKC PKD protein kinase D1 triple-negative breast cancer |